SUMMARY OF WORK The ultimate goals of this project are to determine how arterial stiffness properties influence myocardial structure and function and contribute to cardiovascular morbidity and mortality. A. We have examined the contribution of arterial stiffness to left ventricular (LV) mass in 695 men and 616 women from Taiwan (Contract #N01-AG-02-2118). In both sexes, the major predictors of LV mass were systolic blood pressure, body surface area and age; AGI contributed minimally (r2 less than or equal to 0.006) to LV mass in either sex. B. To determine whether growth hormone or sex steroid supplementation ameliorates arterial stiffness properties in older adults with deficiencies of these substances, we are measuring pulse wave velocity and AGI in men and women aged 65 years and older, before and after hormonal replacement. C. We are testing the hypothesis that 1-2 years of home-based aerobic exercise training can reduce arterial stiffness in the multicenter NIH-sponsored Activities Counseling Trial of 810 subjects 35-75 years old. D. To determine whether aerobic exercise training can reduce the elevated arterial stiffness of older heart failure patients and whether such changes in arterial stiffness are related to training-induced improvement of aerobic performance, we will measure arterial stiffness and peak VO2 before and after a 3 month program of aerobic training. E. A multicenter study to determine whether arterial stiffness is an independent risk factor for cardiovascular events in elderly free-living persons has been initiated in collaboration with the Epidemiology Demography Biometry Program of the intramural NIA. F. Follow-up measurements of arterial stiffness on endurance trained older men and their sedentary age peers, initially studied in 1989-1991 have been obtained to determine whether chronic endurance training attenuates the normal age-associated increase in arterial stiffness. G. Arterial stiffness will be measured in the Pittsburgh, PA site for the Cardiovascular Health Study, a comprehensive characterization of cardiovascular structure and function in community dwelling clinically healthy men and women greater than or equal to 65 years old. Long-term follow-up of this cohort will allow us to examine the prognostic significance of arterial stiffness in an older population. H. The relationship between arterial stiffness and some newly discovered hormones involved in sodium and blood pressure regulation (plasma ouabain-like factor and marinobufagenin) is being examined in BLSA subjects across a large age and blood pressure range. I. We have developed a novel index of arterial function, the Decay Index, defined from the exponential rate of decline in the Doppler internal carotid artery flow rate from peak systole to end-diastole.